U.S. Pat. No. 5,145,843 describes halo-4-phenoxyquinoline compounds as having excellent plant fungicide activity, such as those of formula (1), ##STR1## wherein
R.sup.1 and R.sup.3 are independently halo and R.sup.2 and R.sup.4 are H; or R.sup.3 is halo, R.sup.1 is halo or H, and R.sup.2 and R.sup.4 are H; or R.sup.4 is halo and R.sup.1 to R.sup.3 are H;
A is a phenyl group of formula (2) ##STR2## wherein R.sup.9 to R.sup.13 are independently H, CN, NO.sub.2, OH, halo, (C.sub.1 -C.sub.4)alkyl, (C.sub.2 -C.sub.4)alkanoyl, halo(C.sub.1 -C.sub.7)alkyl, hydroxy(C.sub.1 -C.sub.7)alkyl, (C.sub.1 -C.sub.7)alkoxy, halo(C.sub.1 -C.sub.7)alkoxy, (C.sub.1 -C.sub.7)alkylthio, halo(C.sub.1 -C.sub.7)alkylthio, phenyl, substituted phenyl, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, phenyl(C.sub.1 -C.sub.4)alkyl, substituted phenyl(C.sub.1 -C.sub.4)alkyl, benzoyl, SiR.sup.20 R.sup.21 R.sup.22, or OSiR.sup.20 R.sup.21 R.sup.22 where R.sup.20, R.sup.21, and R.sup.22 are H, a (C.sub.1 -C.sub.6)alkyl group, phenyl, or substituted phenyl, provided that at least one of R.sup.20, R.sup.21, and R.sup.22 is other than H, or R.sup.11 and R.sup.12 or R.sup.12 and R.sup.13 combine to form a carbocyclic ring, and provided that unless all of R.sup.9 to R.sup.13 are H or F, then at least two of R.sup.9 to R.sup.13 are H.
Wherein the foregoing definitions, the term substituted phenyl refers to phenyl substituted with up to three groups selected from halo, (C.sub.1 -C.sub.10)alkyl, halo(C.sub.1 -C.sub.7)alkyl, hydroxy(C.sub.1 -C.sub.7)alkyl, (C.sub.1 -C.sub.7)alkoxy, halo(C.sub.1 -C.sub.7)alkoxy, phenoxy, phenyl, NO.sub.2, OH, CN, (C.sub.1 -C.sub.4)alkanoyloxy, or benzyloxy.
The term alkyl refers to linear, branched, or cyclic alkyl.
The term halo refers to fluoro, chloro, bromo, or iodo.
The term substituted phenoxy refers to a phenoxy group substituted with up to three groups selected from halo, (C.sub.1 -C.sub.10)alkyl, halo(C.sub.1 -C.sub.7)alkyl, hydroxy-(C.sub.1 -C.sub.7)alkyl, (C.sub.1 -C.sub.7)alkoxy, halo(C.sub.1 -C.sub.7)alkoxy, phenoxy, phenyl, NO.sub.2, OH, CN, (C.sub.1 -C.sub.4)alkanoyloxy, or benzyloxy.
The term substituted phenylthio refers to a phenylthio group substituted with up to three groups selected from halo, (C.sub.1 -C.sub.10)alkyl, halo(C.sub.1 -C.sub.7)alkyl, hydroxy(C.sub.1 -C.sub.7)alkyl, (C.sub.1 -C.sub.7)alkoxy, halo(C.sub.1 -C.sub.7)alkoxy, phenoxy, phenyl, NO.sub.2, OH, CN, (C.sub.1 -C.sub.4)alkanoyloxy, or benzyloxy.
As described in U.S. Pat. No.5,145,843 the compounds of formula (1) may be made by condensing a compound of formula (3) ##STR3## wherein R.sup.1 to R.sup.4 are as previously defined, with a compound of the formula (4) EQU HO--A (4)
wherein A is as previously defined. This reaction can be carried out neat, at a temperature in the range of 80-150.degree. C., or preferably 130-140.degree. C.
Many of the quinoline starting materials may be prepared as described in U.S. Pat. No. 5,145,843, and shown in the following reaction scheme below: ##STR4##
In cases where mixtures of isomeric products are obtained, the mixture of substituted 4-quinolines is chlorinated under standard conditions utilizing phosphorous oxychloride, and the isomeric 4-chloroquinolines are separated by liquid chromatography.
U.S. Pat. No. 5,245,036 describes an improvement over this process whereby the coupling step is carried out in the presence of a 4-dialkylaminopyridine catalyst.
Other known methods which may be used for preparing other types of quinoline materials are described as follows:
4-Hydroxyquinolines may be prepared via the Gould-Jacobs reaction of substituted anilines with ethoxymethylene diethylmalonate. J.A.C.S. 61, 2890 (1939). This procedure is also described in detail in Organic Syntheses, vol. 3 (1955), cited above in U.S. Pat. No. 5,145,843, for the preparation of 4,7-dichloroquinoline, which is a useful intermediate for the antimalarial drug chloroquin. Another general procedure is described in Tetrahedron, vol. 41, pp. 3033-3036 (1985).
Kokai Pat. No. Hei 1(1989)-246263 describes a method for producing 5,7-dichloro-4-(2-fluorophenoxy)-quinoline whereby a mixture of 3,5-dichloroaniline and Meldrum's acid is heated to give 4-oxo-5,7-dichloro-1,4-dihydroquinoline, which is reacted with phosphorus oxychloride to give 4,5,7-trichloroquinoline, which is then reacted with 2-fluorophenol to give the final compound.
Kokai Pat. No. Hei 5(1993)-1555856 describes an acrylic acid based route to produce an addition product with 3,5-dichloroaniline, which is then cyclized and oxidized to the corresponding quinoline compound.
Tetrahedron Letters, vol. 35, no. 32 (1994) describes a decarboxylation process to convert camptothecin, a compound which exhibits antineoplastic activity, to mappicine ketone, whose analogs are of interest in medicinal and pharmacological research. The conversion takes place upon extended reflux in DMF. Changing the solvent to triglyme at 200.degree. C. gave a shorter reaction time. However, it is reported this reaction is limited to analogs with an intact a-hydroxylactone structure.